National Medical Journal of China
Volume 94 · Issue 17 · 2014
Natl Med J China
Difficulties and key points of improving the research level of myopia prevention and treatment
Myopia is a refractive error with high incidence in the world, especially in China. The prevalence rate of myopia exceeds 70% among specific people, such as college students, and it is one of the countries with high prevalence rate in the world. In recent years, the age of myopia is becoming advanced, the incidence rate is increasing year by year, and the ocular complications related to myopia are also increasing, such as retinal detachment, macular hemorrhage, cataract and glaucoma, etc., which can not only lead to visual damage, but also lead to blindness in severe cases. Blindness caused by pathological myopia has been one of the main causes of blindness in China and the primary factor of low vision. China is a big country of myopia, and it has more conditions and needs for the research of myopia pathogenesis, so it should play an important role in the research of myopia. However, the pathogenesis of myopia is unknown, and there are no effective interventions and prevention methods aimed at the etiology. If we can find methods or drugs that effectively delay the progression of myopia, it is of great significance to reduce the incidence of myopia and the occurrence of blinding complications, and even to prevent and treat blindness in China.
Analysis on the relationship between adolescent myopia and serum sex hormone
To investigate the quantitative changes of the serum sex hormone levels in juvenile myopia patients.
In January 2013, investigation of wenzhou middle school 822 adolescents, including 432 male patients and 390 female patients were involved in the study Visual acuity ≥ 5 was set as the normal value. The subjects were divided into two groups, the myopia group and the non-myopia group. Chemiluminescence immunoassay analyzer was used to detect the subjects' sex hormone concentration of estradiol (E2), testosterone (T), follicle stimulating hormone (FSH) and luteinizing hormone (LH).
The follicle stimulating hormone and luteinizing hormone of the female patients were significantly higher than those of male counterparts (P<0.01); among the two groups consisting female myopia and non-myopia patients, a significant difference in luteinizing hormone and follicle stimulating hormone was shown (P<0.05); the distinct differences in the level of luteinizing hormone and testosterone level showed in the male myopia group and non-myopia group were of outstanding statistics significance (P<0.01), showing the result that the level of sex hormone in myopia group was higher than that in the non-myopia group.
A close relationship perhaps between the level of sex hormone with gender differences and juvenile myopia is confirmed.
Association of ZNF644, GRM6 and CTNND2 genes polymorphisms with high myopia
To investigate the association of ZNF644, GRM6 and CTNND2 genes with high myopia in Jiangsu Chinese population.
Case-control association study was used in this research. The subjects consisted of 114 high myopia (all eyes AXL≥ 26 mm) and 132 normal control subjects (AXL were 22.0-24.0 mm). Subjects were collected from Affiliated Hospital of Nantong University ophthalmic center. This project was approved by the Ethics Committee of Affiliated Hospital of Nantong University. Fourteen single nucleotide polymorphisms (SNP) of ZNF644, GRM6 and CTNND2 genes were genotyped by TaqMan MGB probes using the real-time PCR system. Chi-square was used to test the allelic and genotypic associations between cases and controls.
ZNF644-rs358695 was associated with high myopia (P=0.03). The frequency of the minor A allele of rs358695 was 41.2% in the high myopia and 50.8% in the controls, indicating a protective role. In genotype frequency analysis, ZNF644-rs358693 was significant difference between cases and controls in dominant model (P=0.04). ZNF644-rs358695 was significant difference between cases and controls in recessive model (P=0.02). In haplotype analysis, ACCG of ZNF644 showed statistical significance between cases and controls (P=0.02). The other 9 SNP of GRM6 and CTNND2 were not associated with high myopia.
ZNF644 gene mutation was associated with high myopia. ZNF644 gene may play a role in the development of high myopia.
Distribution of refraction and ocular biometric parameters in a population of junior middle school children in Anyang of Henan province
To investigate the distribution of spherical equivalent and ocular biometric parameters in a population of grade 7 children in central China.
2 363 grade 7 students of junior high schools were randomly sampled. The students have been examined at baseline and followed up annually. Detailed questionairies and most of the ocular examinations were performed. Spherical equivalent (Seq) was calculated as sphere + 1/2 cylinder from cycloplegic autorefraction. Myopia was defined as spherical equivalent ≤-0.5D, hyperopia as spherical equivalent ≥+ 0.5D and emmetropia between -0.5D and + 0.5D. The Lensar LS900 was used to measure corneal curvatures, axial length and anterior chamber depth. Right eyes results were analyzed.
Among 2 267 children who have the baseline examination, 1 839 children participated the follow up examination(response rate, 81.1%), with an mean age of 14.7 years (range, 12.9-17.6) and male ratio of 48.4%. The mean spherical equivalent refraction was (-2.62±2.19)D. The prevalence rates of myopia, high myopia, emmetropia and hyperopia were 82.7%, 7.1%, 9.8% and 7.5%. The cumulative incidence rates of myopia and high myopia were 47.1% and 4.5% respectively. Axial length, anterior chamber depth, and corneal curvature were normally distributed. The mean axial length, anterior chamber depth, and corneal curvature were (24.8±1.1)mm, (3.18±0.25)mm, (42.8±1.4)D and (43.9±1.6)D respectively. Axial length was longer, anterior chamber depth was deeper, and corneal were flatter in the male(P=0.000). Axial length and anterior chamber depth correlated negatively with refraction.
A moderate myopic distribution of refraction was present in the grade 9 students in central China. The prevalence rates of myopia and high myopia were relatively high in this 14-year-old population compared to other countries. It is necessary to strengthen the prevention of juvenile myopia.
Analysis of prognostic factors for patients with traumatic acute subdural hematomas treated by surgery
To analyze the factors correlated with the surgical prognosis of patients with traumatic acute subdural hematoma (ASDH).
A total of 117 surgical patients for traumatic ASDH between January 2007 and August 2012 were retrospectively reviewed. The clinical factors correlated with prognosis were statistically analyzed. Glasgow outcome score (GOS) was used for prognostic evaluations and favorable prognosis was defined as 4-5 points.
The percentage of patients with favorable prognosis was 43.59% and the mortality 39.32%. The factors correlated with favorable prognosis included age <40 years, pre-operative GCS >8, no pre-operative herniation, duration between injury and surgical depression ≤4 h, without injury of drainage vein, mild brain edema and good brain palpation; the factors correlated with mortality included age >60 years, pre-operative GCS ≤8, pre-operative herniation, duration between injury and surgical depression >4 h, injury of drainage vein, serious brain edema and weak brain palpation Logistic regression confirmed preoperative GCS >8, no preoperative herniation, injury of drainage vein and postoperative good brain palpation were independent factors associated with favorable prognosis.
Patients with age <40 years, preoperative GCS>8, no preoperative herniation, injury of drainage vein and postoperative good brain palpation tend to have favorable prognoses.
Preliminary experiences of "Waffle cone" technique for the treatment of intracranial aneurysm
To explore the preliminary experiences of "Waffle cone" technique for the treatment of intracranial aneurysm.
Retrospective data analyses were performed for patients with intracranial aneurysms embolized by the "Waffle cone" technique from stent-assisted coiling at our hospital from December 2010 to November 2012.
Six patients used the "Waffle cone" technique from 138 stent-assisted coiling. All had complex wide-neck bifurcation cerebral aneurysms. And the angles between parental artery and distal vessels were acute. Six rupture aneurysms were at the terminus of basilar artery (BA) ( n=2), right anterior communicating artery (AcomA) (n=3) and trifurcation middle cerebral artery (MCA) (n=1). All stents were of Solitaire with specification 4×15 mm(ev3, USA). Four patients had Raymond classification Class Ⅰ while another 2 Class Ⅱ. No perioperative complication occurred. The average follow-up period was 6 months.
This technique is safe, time-saving, simple and effective for complex, wide-necked bifurcation aneurysms with acute angles between parental artery and distal vessels. Long-term follow-ups are needed to further evaluate its efficacy.
Study on the heterogeneity of edema in severe preeclampsia
The aim of this study was to analysis the clinical edema forms and explore the heterogeneity of edema in severe preeclampsia(PE).
From February 2002 to February 2009, Peking University Third Hospital admitted with severe preeclampsia 228 cases who were enrolled in this study. The form is divided into no edema (A-type), pure interstitial edema (B-type), a simple cavity gap edema (C-type) and mixed interstitial edema that coexist with lacunar edema (D-type). Analysis and comparison of various types of edema in patients with different clinical manifestations of prenatal care models, laboratory parameters, the incidence of gestational age, complications and obstetric and perinatal outcomes, and analyze the relationship between different types of edema and albumins and the peak value of proteinuria.
Edema was seen in 86% (197/228) of all of cases. Compared the cases who have regular prenatal care with those who have irregular care, differences were statistically significant in edema type composition ratio (P<0.01) and the incidence of serious complications (P<0.01), and serum albumin levels (P<0.01), but not in the peak value of proteinuria (P> 0.05); Compared early-onset PE and late-onset PE patients, differences were statistically significant in edema type composition ratio (P<0.01) and peak value of proteinuria (P<0.01), but not in serum albumin levels and the incidence of serious complications (P>0.05). Comparison between the various types of edema, differences were statistically significant in serum albumin levels and peak value of proteinuria and incidence of serious complications and the gestational week at PE onset and the incidence of treatment preterm labor (P<0.05). Occurrence of placental abruption, heart failure and HELLP syndrome had statistical significance in different types of edema(P<0.05). The varying degrees of interstitial edema were correlated with serum albumin levels (r=-0.19, P<0.05) and serious complication occurrence (r=-0.232, P<0.05), but no correlation displayed with the peak value of urinary protein (P>0.05).
The manifestations of edema were diverse in severe preeclampsia. The forms of edema were related to the PE onset of gestational age and serious complication involving in different organs. Strengthen prenatal care and early detection of edema may improve adverse obstetric outcomes.
Correlation between pelvic indices, pelvic spatial orientation and lumbar vertebrate instability
To explore the correlation between the stability of lumbar vertebrate and pelvic indices of pelvic incidence (PI), lumber lordosis (LL), pelvic tilt (PT) and sacrum slope (SS).
The preoperative imaging data were analyzed retrospectively for 78 patients with lumbar disc protrusion. The values of PI, PT, SS and LL were measured and compared between lumbar vertebrate stability and lumbar vertebrate instability groups.
No inter-group statistical difference existed in PI, LL, PT or SS. The average PI of lumbar vertebrate instability group was higher than that of lumbar vertebrate stability group. In patients with L4/5 segmental lesion, SS of lumbar vertebrate instability group was higher than that of lumbar vertebrate stability group (38.7±4.7)° vs (34.0±6.6)°, P=0.023. And PT in patients with L5/S1 segmental lesion was higher than those with L4/5 segmental lesion (17.5±7.0 vs 14.9±5.3, P=0.027).
No statistical inter-group difference exists in PI. However, higher SS and PT may be risk indicators of instability for L4/5 and L5/S1 segments respectively.
Therapeutic effect of endoscopic third ventriculostomy for pediatric hydrocephalus
To validate the proposed endoscopic third ventriculostomy success score (ETVSS) for predicting successful ETV outcomes for pediatric hydrocephalus on the basis of individual characteristics.
For 121 cases at our department from June 2007 to June 2010 at both 6 and 24 months, Actual successful rates were compared with Chi-square test and 95% confidence interval for low, moderate and high chance of success strata based on the ETVSS. Long-term successful probability was calculated with Kaplan-Meier methods.
The 6-month ETV successful rate was higher than the mean predicted probabilities of success for both moderate and low success strata, but slightly lower for the high chance of success strata. The ETVSS accurately predicted the outcomes at 24 months; the low, medium and high chance of success strata had actual success rates of 74%(37/50), 62%(28/45) and 41%(11/26) and mean predicted successful probabilities of 81.3%, 61.4% and 34.4% respectively.
ETVSS may accurately predict the overall long-term successful rates in high, moderate and low-risk groups. Thus it will aid clinical decision-making through predicting the therapeutic effect of ETV.
Expression and significance of cyclophilin A in synovial fibroblasts from patients with rheumatoid arthritis
To observe the expression of cyclophilin A (CyPA) and the effects of lipopolysaccharide (LPS) on CyPA expression in synovial fibroblasts (SF) from patients with rheumatoid arthritis (RA) and evaluate the potential significance of CyPA in the regulation of the onset and development of inflammation process in RA patients.
SF were separated and cultured from synovial tissues of 12 patients with RA, 9 with osteoarthritis (OA) and 5 with knee trauma. The protein and mRNA expression levels of CyPA in SF were detected by Western blot (WB) and real-time quantitative polymerase chain reaction (RT-qPCR) respectively. Correlation analysis was conducted between the protein expression of CyPA in SFs and clinical parameters. Then the effects of LPS on CyPA in SF from 3 groups were detected.
The expression levels of CyPA protein and mRNA in RA group were 0.86±0.47 and 0.54±0.22 respectively, significantly higher than those in OA group (0.40±0.31 and 0.03±0.02, P<0.05) and trauma group (0.34±0.21 and 0.03±0.01,P<0.05). The protein expression level of CyPA in SF of RA group had positive correlations with erythroeyte sedimentation rate (ESR), rheumatoid factor (RF) and swelling joint counts (SJC) (P<0.05). After LPS treatment, CyPA protein and mRNA levels were 2.65±1.16 and 1.82±0.39 in RA SF and they were significantly higher than those in RA SF without LPS treatment (P<0.05). The CyPA expression of SF from OA and trauma groups slightly decreased after LPS treatment. However the differences were not statistically significant (P>0.05).
The expression of CyPA is up-regulated in SF and it is positively correlated with ESR, RF and SJC in RA patients. It indicates that CyPA may be involved in the regulation of the onset and development of inflammation process of RA. And LPS may promote the expression of CyPA in SF of RA patients.
Mid-term outcomes of unilateral pedicle screw fixation with lumbar interbody fusion for lumber degenerative diseases
To evaluate the mid-term clinical outcomes of unilateral pedicle screw fixation with lumbar interbody fusion for lumber degenerative diseases.
From October 2008 to December 2010, unilateral pedicle screw fixation with lumbar interbody fusion was performed for a consecutive cohort of 42 patients. There were 18 males and 24 females with an average age of 52 (38-69) years. The operation level at L3-4 (n=2), L4-5 (n=19), L5-S1 (n=21) and multilevel (n=0). Their clinical outcomes were assessed by Oswestry (ODI) scores and Japanese Orthopedics Association (JOA) questionnaires before and after operation. Operative duration, intraoperative blood loss, incision status and complications were recorded. Radiological examination was performed to assess the height of intervertebral space, the postoperative intervertebrai fusion conditions and the degeneration of adjacent segments.
The mean operative duration was 90 minutes and mean blood loss 150 ml. All incisions healed primarily. The mean follow-up period was 40 (36-58) months. The ODI scores decreased significantly from 59.1±9.6 preoperatively to 8.5±2.7 postoperatively (P<0.05). The JOA scores improved markedly from 8.3±2.7 preoperatively to 23.3±2.1 postoperatively (P<0.05). And the proportion of optimal outcomes was 88.1%. The ventral and dorsal heights of intervertebal disc were significantly higher than those before operation. The fusion rate was 95.2% and the incidence of adjacent segment degeneration 9.5%. There was no occurrence of such complications as secondary scoliosis, screw loosening, internal fixation failure and cage slippage.
Unilateral pedicle screw fixation with lumbar interbody fusion is efficacious for lumber degenerative diseases with little surgical trauma.
Surgical correction of congenital vertical talus by one-stage comprehensive soft-tissue release and peritalar reduction incorporating tibialis anterior transfer
To evaluate the surgical efficacies of one-stage comprehensive soft-tissue release and peritalar reduction incorporating tibialis anterior transfer(CSTR-PTR-TAT)in patients with congenital vertical talus (CVT) before the age of 4 years.
Thirty-five feet of 21 children with true congenital vertical talus were underwent one-stage CSTR-PTR-TAT. The male-to-female ratio was 2.5∶1. Twenty-three percent (5 patients with 8 feet) belonged to isolated CVT and the remaider CVT associated with other congenital or neuromuscular abnormalities. The mean operative age was 30.1 (12-48) months. All patients were available for clinical and radiological follow-ups for a mean period of 3.5 (1.5-7) years. Kodros scoring system was utilized for assessment of final outcomes.
The outcomes of 3 feet (9%) were excellent, 27 (77%) good and 5 (14%) fair. All patients wore normal shoes and were satisfied by their functional results and appearance. The patients with fair results were associated with arthrogryposis. No talar avascular necrosis was encountered. None required further operation. Radiologically there was a statistically significant postoperative improvement of measured angles compared to preoperative values (P<0.05). All radiological parameters were within normal ranges. There was no difference of posoperative angles compared to those at the final follow-up (P>0.05).
As a complex deformity usually associated with other congenital or neuromuscular abnormalities, CVT may be satisfactorily managed with one-stage correction by CSTR-PTR-TAT before the age of 4 years.
Comparative study of endorectal ultrasonography and magnetic resonance imaging in preoperative staging of rectal cancer
To evaluate the diagnostic value of endorectal ultrasonography (ERUS) and magnetic resonance imaging (MRI) in preoperative staging of rectal carcinoma.
A total of 44 patients with biopsy proven rectal tumor underwent preoperative ERUS and MRI examinations. All patients were evaluated to determine the diagnostic accuracy of depth of transmural tumor invasion and lymph node metastases. Imaging results were compared with histopathological findings.
The accuracy of T staging (uT1, uT2, uT3, uT4) for ERUS was 95.5%, 90.9%, 93.2% and 97.7% and the overall accuracy 88.6%(39/44). The sensitivity was 83.3%, 72.7%, 72.2%, 77.8% and the specificity 97.3%, 92.9%, 96.2% and 97.6%. The accuracy of T staging (T1, T2, T3, T4) for MRI was 93.2%, 90.9%, 93.2%, 100.0% and the overall accuracy 86.4%(38/44). The sensitivity was 71.4%, 93.8%, 94.4% and 100.0% and the specificity 97.3%, 89.3%, 92.3% and 100.0%. Detection of lymph node metastases: the accuracy of ERUS was 75.0%(33/44), MRI 93.2%(41/44). The sensitivity and specificity was found to be 68.4%(13/19) and 80.0%(20/25)on ERUS, 94.7%(18/19) and 92.0%(23/25)on MRI respectively.
ERUS and MRI may be used for accurate preoperative staging of rectal cancer. ERUS has higher accuracy and sensitivity for T1 stage while MRI is preferred for lymph node metastasis.
Computed tomography-guided percutaneous microwave ablation for diaphragm-abutting liver tumors: assessments of safety and short-term therapeutic efficacies
To assess the safety and short-term therapeutic efficacies of computed tomography (CT)-guided percutaneous microwave ablation (PMA) for diaphragm-abutting liver tumors.
A total of 69 patients with 75 diaphragm-abutting liver tumors (tumor from diaphragmc ≤5 mm) underwent CT-guided PMA. According to the site of diaphragm-abutting lesions, they were divided into neighboring muscle group (group A) and neighboring aponeurosis group (group B); According to the size of lesions, they were divided into <2.5 cm group (group Ⅰ) and ≥2.5 cm group (group Ⅱ). The complications of intra and post-ablation within 2 weeks were recorded. They underwent contrast enhanced CT (CECT) or contrast enhanced MRI (CEMRI) at Month 1, 3 and 6 post-ablation. Then CEMRI or CECT was re-checked every 3-6 months. All patients were followed up for 12-30 months. Comparative analyses were performed for short-term therapeutic efficacies.
At Month 1 post-PMA, complete response (CR) rate was 86.7% (65/75) and incomplete response (ICR) rate 13.3% (10/75). After additional ablation, 5 lesions transformed into CR. No statistical difference in CR rate existed between groups A and B (95.0% vs 77.1%). The CR rate of group Ⅰ was obviously higher than that of group Ⅱ (95.0% vs 77.1%). The 1-year survival rate was 97.1%. The occurring rate of minor complications was 42.0% (29/69) and that of serious complications 2.9% (2/69). No statistical difference of occurring rates of minor complications existed between groups A and B(38.1%vs 45.5%). But the occurring rates of diaphragmatic burns, pulmonary exudation and pneumothorax had obvious statistical differences between two groups. The occurring rate of minor complications in group Ⅰ was obviously lower than that of group Ⅱ (30.0% vs 54.3%) and serious complications occurred in group Ⅱ. Minor complications were reversible and recovered after non-special or symptomatic treatment. Two cases of serious complications improved after standard clinical treatment.
CT-guided PMA for diaphragm-abutting liver tumors is both safe and effective. However puncture route and power/time should be optimized according to tumor size and location.
Effects of mild hypothermia plus ifenprodil on apoptosis inducing factor translocation after global cerebral ischemia-reperfusion in rats
To explore the effects of mild hypothermia combined with ifenprodil on the survival of neuronal and translocation of apoptosis inducing factor (AIF) following global cerebral ischemia-reperfusion to understand the mechanism of combination in cerebral resuscitation.
Eighty male SD rats were randomly divided into 5 groups of sham (Ⅰ), model (Ⅱ), ifenprodil (Ⅲ), mild hypothermia (Ⅳ) and ifenprodil plus mild hypothermia (Ⅴ) (n=16 each). Group Ⅰ completed all procedures except for ventricular fibrillation (VF) and cardio pulmonary resuscitation (CPR). For groups Ⅱ and Ⅴ, the model of global cerebral ischemia-reperfusion was established and VF induced with transoesophageal cardiac pacing; groups Ⅲ and Ⅴ received by an intraperitoneal injection of ifenprodil immediately after reperfusion and other groups had an equal volume of distilled water. Rectal temperature was cooled down to (32±1)℃ in groups Ⅳ and Ⅴ by rubbing body surface with ethanol in 10 min after reperfusion and maintained 4 hours continuously while other groups at (37±1)℃. In hippocampal CA1 region at 24 hours after reperfusion, the pathomorphological changes and quantity of pyramidal cells were detected with hematoxylin and eosin staining, nuclear translocation of AIF was shown with immunofluorescence technique and the nuclear expression level of AIF was measured with Western blot.
Compared with group Ⅰ (75.0±3.2), the number of pyramidal cells decreased in other groups (P<0.05); compared with group Ⅱ (36.0±1.2), the number increased in group Ⅲ(46.8±1.3), Ⅳ(49.0±2.7)and Ⅴ(61.3±2.60)(P<0.05). In particular, cell count increased significantly in group Ⅴ (P<0.05). Compared to group Ⅰ, the transloctation of AIF form mitochondria to nucleus was detected in other groups; compared with group Ⅰ(0.022±0.003), the expression level of AIF in the nucleus was higher in other groups (P<0.05). Compared with group Ⅱ(1.020±0.029), the expression levels of AIF in groups Ⅲ(0.870±0.016), Ⅳ(0.820±0.050)and Ⅴ(0.550±0.050)were lower (P<0.05). And it decreased significantly in group Ⅴ (P<0.05).
Mild hypothermia plus ifenprodil may alleviate neuronal damage after global cerebral ischemia/reperfusion injury through mitigating its pro-apoptotic role after AIF translocation.
Effect of percutaneous vertebroplasty on osteoporotic vertebral compression fracture
Vertebroplasty (VP) is the injection of bone cement or other bone materials through the vertebral pedicle or directly into the vertebral body to relieve pain and increase the mechanical strength of the diseased vertebra. After percutaneous vertebroplasty (PVP) for the treatment of vertebral hemangioma[
A case of anti-N-methyl-D-aspartate receptor encephalitis with prominent manifestation of muscle twitching
The patient was a 21-year-old female. He was admitted to hospital on March 29, 2013 with the main complaint of "headache for more than 20 days, right hand shaking, facial muscle twitching for more than 10 days, and salivation for 1 day". The patient experienced poor sleep and headache 20 days before seeing the doctor. The local hospital gave "Anshen Bu Nao Liquid" and "Vitamin B1" orally, but the symptoms did not improve significantly. More than 10 days ago, the patient experienced involuntary shaking of his right hand and involuntary twitching of his right facial muscles. When he was nervous, his speech was still clear, and the symptoms of "acupuncture" treatment were not relieved. That night, the patient experienced delirium, so he went to Henan Psychiatric Hospital, where he was diagnosed with "(1) schizophrenia and (2) viral encephalitis". He was given symptomatic supportive treatment such as antiviral (details unknown), but the symptoms did not improve. For further diagnosis and treatment, I went to the First Affiliated Hospital of Zhengzhou University. Physical examination: confusion, general spirit, unclear speech, inability to cooperate with advanced intelligent activities, bilateral pupils of equal size and round, with a diameter of 3 mm, sensitive to light reflection, inability to cooperate with the examination of remaining cranial nerves, and increased muscle tone of limbs. Extremity tendon reflex (+ +), neck strong, Kernig sign negative, Brudzinski sign negative. The bilateral pathological signs were not drawn out, and the physical examination of the remaining nervous system could not cooperate. Skull MRI: (1) Mild white matter demyelination in bilateral frontal lobes (
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